International nonproprietary name

The World Health Organization has a constitutional mandate to "develop, establish and promote international standards with respect to biological, pharmaceutical and similar products".

The World Health Organization collaborates closely with INN experts and national nomenclature committees to select a single name of worldwide acceptability for each active substance that is to be marketed as a pharmaceutical. To avoid confusion, which could jeopardize the safety of patients, trade-marks should neither be derived from INNs nor contain common stems used in INNs.

Having unambiguous standard names for each drug (standardization of drug nomenclature) is important because a drug may be sold by many different brand names, or a branded medication may contain more than one drug, for example, the branded medications Celexa, Celapram and Citrol all contain the same active ingredient: citalopram; and the branded preparation Lemsip contains two active ingredients: paracetamol and phenylephrine.

The WHO issues INNs in English, Latin, French, Russian, Spanish, Arabic, and Chinese, and a drug's INNs are often cognate across most or all of the languages, with minor spelling or pronunciation differences, for example: paracetamol (en) paracetamolum (la), paracétamol (fr) and парацетамол (ru). An established INN is known as a recommended INN (rINN), while a name that is still being considered is called a proposed INN (pINN).

Drugs from the same therapeutic or chemical class are usually given names with the same stem. Stems are mostly placed word-finally, but in some cases word-initial stems are used, they are collected in a publication informally known as the Stem Book.[3]

The term stem is not used consistently in linguistics, it has been defined as a form to which affixes (of any type) can be attached.[4] Under a different and apparently more common view, this is the definition of a root,[5] while a stem consists of the root plus optional derivational affixes, meaning that it is the part of a word to which inflectional affixes are added.[6] INN stems employ the first definition, while under the more common alternative they would be described as roots.

Pharmacology and pharmacotherapy (like health care generally) are universally relevant around the world, making translingual communication about them an important goal. An interlingual perspective is thus useful in drug nomenclature, the WHO issues INNs in English, Latin, French, Russian, Spanish, Arabic, and Chinese. A drug's INNs are often cognates across most or all of the languages, but they also allow small inflectional, diacritic, and transliterational differences that are usually transparent and trivial for nonspeakers (as is true of most international scientific vocabulary). For example, although paracetamolum (la) has an inflectional difference from paracetamol (en), and although paracétamol (fr) has a diacritic difference, the differences are trivial; users can easily recognize the "same word". And although парацетамол (ru) and paracetamol (en) have a transliterational difference, they sound similar, and for Russian speakers who can recognize Latin script or English speakers who can recognize Cyrillic script, they look similar; users can recognize the "same word". Thus INNs make medicines bought anywhere in the world as easily identifiable as possible to people who do not speak that language. Notably, the "same word" principle allows health professionals and patients who do not speak the same language to communicate to some degree and to avoid potentially life-threatening confusions from drug interactions.

A number of spelling changes are made to British Approved Names and other older nonproprietary names with an eye toward interlingual standardization of pronunciation across major languages,[7] thus a predictable spelling system, approximating phonemic orthography, is used, as follows:

Many drugs are supplied as salts, with a cation and an anion, the way the INN system handles these is explained by the WHO at its "Guidance on INN" webpage.[2] For example, amfetamine and oxacillin are INNs, whereas various salts of these compounds – e.g., amfetamine sulfate and oxacillin sodium – are modified INNs (INNM).[2][8]

Several countries had created their own nonproprietary naming system before the INN was created, and in many cases, the names created under the old systems continue to be used in those countries, as one example, in English the INN name for a common painkiller is paracetamol; the table below gives the alternative names for this in different systems:

^"Guidelines on the Use of International Nonproprietary Names (INNS) for Pharmaceutical Substances". World Health Organization. 1997. Retrieved 1 December 2014. In principle, INNs are selected only for the active part of the molecule which is usually the base, acid or alcohol. In some cases, the active molecules need to be expanded for various reasons, such as formulation purposes, bioavailability or absorption rate; in 1975, the experts designated for the selection of INN decided to adopt a new policy for naming such molecules. In future, names for different salts or esters of the same active substance should differ only with regard to the inactive moiety of the molecule. ... The latter are called modified INNs (INNMs).

1.
World Health Organization
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The World Health Organization is a specialised agency of the United Nations that is concerned with international public health. It was established on 7 April 1948, headquartered in Geneva, the WHO is a member of the United Nations Development Group. Its predecessor, the Health Organization, was an agency of the League of Nations, the constitution of the World Health Organization had been signed by 61 countries on 22 July 1946, with the first meeting of the World Health Assembly finishing on 24 July 1948. It incorporated the Office international dhygiène publique and the League of Nations Health Organization, since its creation, it has played a leading role in the eradication of smallpox. The WHO is responsible for the World Health Report, an international publication on health, the worldwide World Health Survey. The head of WHO is Margaret Chan, the 2014/2015 proposed budget of the WHO is about US$4 billion. About US$930 million are to be provided by member states with a further US$3 billion to be from voluntary contributions, after failing to get a resolution passed on the subject, Alger Hiss, the Secretary General of the conference, recommended using a declaration to establish such an organisation. Dr. Sze and other delegates lobbied and a declaration passed calling for a conference on health. The use of the world, rather than international, emphasised the truly global nature of what the organisation was seeking to achieve. The constitution of the World Health Organization was signed by all 51 countries of the United Nations and it thus became the first specialised agency of the United Nations to which every member subscribed. Its constitution formally came into force on the first World Health Day on 7 April 1948, the first meeting of the World Health Assembly finished on 24 July 1948, having secured a budget of US$5 million for the 1949 year. Andrija Stampar was the Assemblys first president, and G. Brock Chisholm was appointed Director-General of WHO and its first priorities were to control the spread of malaria, tuberculosis and sexually transmitted infections, and to improve maternal and child health, nutrition and environmental hygiene. Its first legislative act was concerning the compilation of statistics on the spread. The logo of the World Health Organization features the Rod of Asclepius as a symbol for healing, in 1947 the WHO established an epidemiological information service via telex, and by 1950 a mass tuberculosis inoculation drive using the BCG vaccine was under way. In 1955, the eradication programme was launched, although it was later altered in objective. 1965 saw the first report on diabetes mellitus and the creation of the International Agency for Research on Cancer. In 1958, Viktor Zhdanov, Deputy Minister of Health for the USSR, called on the World Health Assembly to undertake an initiative to eradicate smallpox. At this point,2 million people were dying from smallpox every year, in 1966, WHO moved into its headquarters building

2.
Brand
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A brand is a name, term, design, symbol, or other feature that distinguishes one seller’s product from those of others. Brands are used in business, marketing, and advertising, however, the term has been extended to mean a strategic personality for a product or company, so that ‘brand’ now suggests the values and promises that a consumer may perceive and buy into. Branding is a set of marketing and communication methods that help to distinguish a company from competitors, the key components that form a brands toolbox include a brand’s identity, brand communication, brand awareness, brand loyalty, and various branding strategies. Brand equity is the totality of a brands worth and is validated by assessing the effectiveness of these branding components. To reach such an invaluable brand prestige requires a commitment to a way of doing business. A corporation who exhibits a strong brand culture is dedicated on producing intangible outputs such as customer satisfaction, reduced price sensitivity and customer loyalty. A brand is in essence a promise to its customers that they can expect long-term security, when a customer is familiar with a brand or favours it incomparably to its competitors, this is when a corporation has reached a high level of brand equity. Many companies are beginning to understand there is often little to differentiate between products in the 21st century. Branding remains the last bastion for differentiation, in accounting, a brand defined as an intangible asset is often the most valuable asset on a corporation’s balance sheet. The word ‘brand’ is often used as a referring to the company that is strongly identified with a brand. Marque or make are often used to denote a brand of motor vehicle, a concept brand is a brand that is associated with an abstract concept, like breast cancer awareness or environmentalism, rather than a specific product, service, or business. A commodity brand is a associated with a commodity. The word, brand, derives from Dutch brand meaning to burn and this product was developed at Dhosi Hill, an extinct volcano in northern India. Roman glassmakers branded their works, with Ennion being the most prominent, the Italians used brands in the form of watermarks on paper in the 13th century. Blind Stamps, hallmarks, and silver-makers marks are all types of brand, industrialization moved the production of many household items, such as soap, from local communities to centralized factories. When shipping their items, the factories would literally brand their logo or insignia on the barrels used, Bass & Company, the British brewery, claims their red-triangle brand as the worlds first trademark. Another example comes from Antiche Fornaci Giorgi in Italy, which has stamped or carved its bricks with the same proto-logo since 1731, cattle-branding has been used since Ancient Egypt. The term, maverick, originally meaning an un-branded calf, came from a Texas pioneer rancher, Sam Maverick, use of the word maverick spread among cowboys and came to apply to unbranded calves found wandering alone

3.
Pharmaceutical drug
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A pharmaceutical drug is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy is an important part of the field and relies on the science of pharmacology for continual advancement. Drugs are classified in various ways, one of the key divisions is by level of control, which distinguishes prescription drugs from over-the-counter drugs. Other ways to classify medicines are by mode of action, route of administration, biological system affected, an elaborate and widely used classification system is the Anatomical Therapeutic Chemical Classification System. The World Health Organization keeps a list of essential medicines, Drug discovery and drug development are complex and expensive endeavors undertaken by pharmaceutical companies, academic scientists, and governments. Governments generally regulate what drugs can be marketed, how drugs are marketed, controversies have arisen over drug pricing and disposal of used drugs. In the US, a drug is, A substance recognized by an official pharmacopoeia or formulary, a substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease. A substance intended to affect the structure or any function of the body, a substance intended for use as a component of a medicine but not a device or a component, part or accessory of a device. Pharmaceutical or a drug is classified on the basis of their origin, Drug from natural origin, Herbal or plant or mineral origin, some drug substances are of marine origin. Drug from chemical as well as origin, Derived from partial herbal and partial chemical synthesis Chemical. Drug derived from animal origin, For example, hormones, Drug derived from microbial origin, Antibiotics Drug derived by biotechnology genetic-engineering, hybridoma technique for example Drug derived from radioactive substances. An elaborate and widely used system is the Anatomical Therapeutic Chemical Classification System. The World Health Organization keeps a list of essential medicines, the main classes of painkillers are NSAIDs, opioids and Local anesthetics. For consciousness Some anesthetics include Benzodiazepines and Barbiturates, the main categories of drugs for musculoskeletal disorders are, NSAIDs, muscle relaxants, neuromuscular drugs, and anticholinesterases. Euthanasia is not permitted by law in countries, and consequently medicines will not be licensed for this use in those countries. Administration is the process by which a patient takes a medicine, there are three major categories of drug administration, enteral, parenteral, and other. It can be performed in various forms such as pills, tablets. There are many variations in the routes of administration, including intravenous and they can be administered all at once as a bolus, at frequent intervals or continuously

4.
Medical prescription
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A prescription is a health-care program implemented by a physician or other qualified health care practitioner in the form of instructions that govern the plan of care for an individual patient. The term often refers to a health care providers written authorization for a patient to purchase a prescription drug from a pharmacist, Prescriptions may be entered into an electronic medical record system and transmitted electronically to a pharmacy. Alternatively, a prescription may be handwritten on preprinted prescription forms that have been assembled into pads, in some cases, a prescription may be transmitted from the physician to the pharmacist orally by telephone, this practice may increase the risk of medical error. The content of a prescription includes the name and address of the prescribing provider, unique for each prescription is the name of the patient. In the United Kingdom and Ireland, the name and address must also be recorded. Each prescription is dated and some jurisdictions may place a limit on the prescription. Prescriptions also contain directions for the patient to follow when taking the drug and these directions are printed on the label of the pharmaceutical product. ℞ is a symbol meaning prescription and it is sometimes transliterated as Rx or just Rx. This symbol originated in medieval manuscripts as an abbreviation of the Late Latin verb recipe, medieval prescriptions invariably began with the command to take certain materials and compound them in specified ways. Folk theories about the origin of the symbol ℞ note its similarity to the Eye of Horus, or to the ancient symbol for Zeus or Jupiter, gods whose protection may have been sought in medical contexts. The word prescription, from pre- and script, refers to the fact that the prescription is an order that must be written down before a drug can be prepared. Those within the industry will often call prescriptions simply scripts, jurisdictions may adopt a statutory definition of prescription that applies as a term of art only to the operation of that statute, but the general legal definition of the word is this broad one. Many brand name drugs have cheaper generic drug substitutes that are therapeutically and biochemically equivalent, Prescriptions will also contain instructions on whether the prescriber will allow the pharmacist to substitute a generic version of the drug. This instruction is communicated in a number of ways, in some jurisdictions, the preprinted prescription contains two signature lines, one line has dispense as written printed underneath, the other line has substitution permitted underneath. Some have a preprinted box dispense as written for the prescriber to check off, in other jurisdictions they may use completely different languages, never mind a different formula of words. In some jurisdictions, it may be a requirement to include the age of child on the prescription. For pediatric prescriptions some advise the inclusion of the age of the if the patient is less than twelve. Adding the weight of the child is also helpful, Prescriptions often have a label box

5.
Standardization
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It can also facilitate commoditization of formerly custom processes. This view includes the case of spontaneous standardization processes, to de facto standards. Standard weights and measures were developed by the Indus Valley Civilisation, weights existed in multiples of a standard weight and in categories. Technical standardisation enabled gauging devices to be used in angular measurement and measurement for construction. Uniform units of length were used in the planning of such as Lothal, Surkotada, Kalibangan, Dolavira, Harappa. The weights and measures of the Indus civilisation also reached Persia and Central Asia, Standardisation is also related to Processes. In view of large variations in units related to Civil, Electrical and other Engineering streams, engineers united to overcome the situation and this association later on gave birth to ISO in 1950. ISO stands for International Organisation for Standardisation and this voluntary organisation is solely dedicated to standardisation and makes standards related to it. Certification as per ISO norms is popular all across world, henry Maudslay developed the first industrially practical screw-cutting lathe in 1800. This allowed for the standardisation of screw thread sizes for the first time, before this, screw threads were usually made by chipping and filing. Nuts were rare, metal screws, when made at all, were usually for use in wood, metal bolts passing through wood framing to a metal fastening on the other side were usually fastened in non-threaded ways. This was an advance in workshop technology. Maudslays work, as well as the contributions of other engineers, accomplished a modest amount of industry standardization, joseph Whitworths screw thread measurements were adopted as the first national standard by companies around the country in 1841. It came to be known as the British Standard Whitworth, and was adopted in other countries. This new standard specified a 55° thread angle and a depth of 0. 640327p and a radius of 0. 137329p. The thread pitch increased with diameter in steps specified on a chart, an example of the use of the Whitworth thread is the Royal Navys Crimean War gunboats. These were the first instance of mass-production techniques being applied to marine engineering, American Unified Coarse was originally based on almost the same imperial fractions. The Unified thread angle is 60° and has flattened crests, thread pitch is the same in both systems except that the thread pitch for the 1⁄2 in bolt is 12 threads per inch in BSW versus 13 tpi in the UNC

6.
Drug nomenclature
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Drug nomenclature is the systematic naming of drugs, especially pharmaceutical drugs. Generic names for drugs are nowadays constructed out of affixes and stems that classify the drugs into different categories, a marketed drug might also have a company code or compound code. The chemical names are the names, based on the molecular structure of the drug. There are various systems of nomenclature and thus various chemical names for any one substance. The most important is the IUPAC name, chemical names are typically very long and too complex to be commonly used in referring to a drug. Sometimes, a company that is developing a drug might give the drug a company code, for example, CDP870 is UCB’s company code for Cimzia. Many of these codes, although not all, have prefixes that correspond to the company name, during development, the company will apply for regulatory approval of the drug by the relevant national regulatory agency, and it will apply for a generic name for that country. It will also apply for an International Nonproprietary Name through the World Health Organization, nowadays the national nonproprietary names are usually the same as the INN. The generic names usually indicate via their stems what drug class the drug belongs to, for example, one can tell that aciclovir is an antiviral drug because its name ends in the -vir suffix. Otherwise the 2 names are both given, joined by hyphens or slashes. For example, suspensions combining trimethoprim and sulfamethoxazole are called either trimethoprim/sulfamethoxazole or co-trimoxazole, similarly, co-codamol is codeine-acetaminophen, and co-triamterzide is triamterene-hydrochlorothiazide. The USP ceased maintaining PENs, but the similar co-prefixed BANs are still current, for drugs that make it all the way through development, testing, and regulatory acceptance, the pharmaceutical company then gives the drug a trade name. The term trade name is a term in the pharmaceutical industry for a brand name or trademark name. For example, Lipitor is Pfizers trade name for atorvastatin, a cholesterol-lowering medication, Drug names are often subject to legal regulation, including approval for new drugs and on packaging to establish clear rules about adulterants and fraudulent or misleading labelling. A national formulary is often designated to define drug names for regulatory purposes, unbiased mentions of a drug place the nonproprietary name first and follow it with the trade name in parentheses, if relevant. This pattern is important for the literature, where conflict of interest is disclosed or avoided. The authors reporting on a study are not endorsing any particular brand of drug and they will often state which brand was used, for methodologic validity, but they do so in a way that makes clear the absence of endorsement. For example, the 2015 American Society of Hematology publication policies say, Non-proprietary names should be used and he first letter of the name of a proprietary drug should be capitalized

7.
Phenylephrine
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Phenylephrine is a selective α1-adrenergic receptor agonist of the phenethylamine class used primarily as a decongestant, as an agent to dilate the pupil, and to increase blood pressure. Phenylephrine can also cause a decrease in heart rate through reflex bradycardia, Phenylephrine is used as a decongestant sold as an oral medicine or as a nasal spray. It is an ingredient in over-the-counter decongestants in the United States. Other decongestants include oxymetazoline and pseudoephedrine, Phenylephrine is used as an alternative for pseudoephedrine in decongestant medicines due to pseudoephedrines use in the illicit manufacture of methamphetamine. Its efficacy as an oral decongestant has been questioned, with several recent independent studies finding that it provided no relief to sinus congestion than a placebo. A2007 meta-analysis by Hatton et al, a 2007 study by Wyeth Consumer Healthcare notes that 7 studies available in 1976 support the efficacy of phenylephrine at a 10 mg dosage. Two studies published in 2009 examined the effects of phenylephrine on symptoms of allergic rhinitis by exposing sufferers to pollen in a controlled, neither study was able to distinguish between the effects of phenylephrine or a placebo. Pseudoephedrine and loratadine-montelukast therapy were found to be more effective than both phenylephrine and placebo. The Food and Drug Administration has stood by its 1976 approval of phenylephrine for nasal congestion as the debate continues, hemorrhoids are caused by swollen veins in the rectal area. Phenylephrine can be used topically to prevent symptoms of hemorrhoids, Phenylephrine causes the constriction of vascular smooth muscle and is often used in the treatment of hemorrhoids presumably to narrow the swollen veins and relieve the attendant pain. However, veins—unlike arteries—contain less vascular smooth muscle in their walls so the mechanism by which relief is achieved is likely related to something other than vascular change alone. Products for treatment may include substances that will form a protective barrier over the inflamed area. Phenylephrine is used as an eye drop to dilate the pupil to facilitate visualization of the retina and it is often used in combination with tropicamide as a synergist when tropicamide alone is not sufficient. Narrow-angle glaucoma is a contraindication to phenylephrine use, as a mydriatic, it is available in 2. 5% and 10% minims. Phenylephrine eye drops are applied to the eye after a topical anesthetic is applied, Phenylephrine is commonly used as a vasopressor to increase the blood pressure in unstable patients with hypotension, especially resulting from septic shock. The elimination half life of phenylephrine is about 2.5 to 3.0 hours, the clinical effects of a single intravenous bolus dose of phenylephrine are short lived and needs to be repeated every 10–15 minutes. Commonly the drug is given as a carefully titrated intravenous infusion with a pump or volumetric pump. Because of its effect, phenylephrine can cause severe necrosis if it infiltrates the surrounding tissues

8.
Propranolol
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Propranolol is a medication of the beta blocker type. It is used to high blood pressure, a number of types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, performance anxiety. It is used to prevent migraine headaches, and to prevent further problems in those with angina or previous heart attacks. It can be taken by mouth or by injection into a vein, the formulation that is taken by mouth comes in short acting and long acting versions. Propranolol appears in the blood after 30 minutes and has an effect between 60 and 90 minutes when taken by mouth. Common side effects include nausea, abdominal pain, and constipation and it should not be used in those with an already slow heart rate and most of those with heart failure. Quickly stopping the medication in those with coronary artery disease may worsen symptoms and it may worsen the symptoms of asthma. Greater care is recommended in those with liver or kidney problems, Propranolol may cause harmful effects in the baby if taken during pregnancy. Its use during breastfeeding is safe, but the baby should be monitored for side effects. It is a beta blocker which works by blocking β-adrenergic receptors. It is on the World Health Organizations List of Essential Medicines, Propranolol is available as a generic medication. The wholesale cost in the world is between 0.24 and 2.16 USD per month as of 2014. In the United States it costs about 15 USD per month at a typical dose and it is occasionally used to treat performance anxiety. Evidence to support the use in other anxiety disorders is poor, Propranolol works to inhibit the actions of norepinephrine, a neurotransmitter that enhances memory consolidation. Individuals given propranolol immediately after trauma experienced fewer stress-related symptoms and lower rates of PTSD than respective control groups who did not receive the drug and this treatment shows promise as being superior to corticosteroids when treating IHs. Extensive clinical case evidence and a controlled trial support its efficacy. Dreaming was reduced and increased awakening, adverse drug reactions associated with propranolol therapy are similar to other lipophilic beta blockers. β-blocking agents in general reduce perfusion of the placenta which may lead to adverse outcomes for the neonate, including pulmonary or cardiac complications, the newborn may experience additional adverse effects such as hypoglycemia and bradycardia

9.
New Latin
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New Latin was a revival in the use of Latin in original, scholarly, and scientific works between c.1375 and c. Modern scholarly and technical nomenclature, such as in zoological and botanical taxonomy and international scientific vocabulary, in such use, New Latin is often viewed as still existing and subject to new word formation. As a language for full expression in prose or poetry, however, classicists use the term Neo-Latin to describe the Latin that developed in Renaissance Italy as a result of renewed interest in classical civilization in the 14th and 15th centuries. Neo-Latin also describes the use of the Latin language for any purpose, scientific or literary, during, the term New Latin came into widespread use towards the end of the 1890s among linguists and scientists. New Latin was, at least in its days, an international language used throughout Catholic and Protestant Europe. Russias acquisition of Kiev in the later 17th century introduced the study of Latin to Russia, though Latin and New Latin are considered extinct, large parts of their vocabulary have seeped into English and several Germanic languages. New Latin was inaugurated by the triumph of the humanist reform of Latin education, led by writers as Erasmus, More. Medieval Latin had been the working language of the Roman Catholic Church, taught throughout Europe to aspiring clerics. It was a language, full of neologisms and often composed without reference to the grammar or style of classical authors. Attempts at reforming Latin use occurred sporadically throughout the period, becoming most successful in the mid-to-late 19th century, the Protestant Reformation, though it removed Latin from the liturgies of the churches of Northern Europe, may have advanced the cause of the new secular Latin. Classic works such as Newtons Principia Mathematica were written in the language, throughout this period, Latin was a universal school subject, and indeed, the pre-eminent subject for elementary education in most of Europe and other places of the world that shared its culture. All universities required Latin proficiency to obtain admittance as a student, Latin was an official language of Poland—recognised and widely used between the 9th and 18th centuries, commonly used in foreign relations and popular as a second language among some of the nobility. As an auxiliary language to the local vernaculars, New Latin appeared in a variety of documents, ecclesiastical, legal, diplomatic, academic. As late as the 1720s, Latin was still used conversationally, for instance, the Hanoverian king George I of Great Britain, who had no command of spoken English, communicated in Latin with his Prime Minister Robert Walpole, who knew neither German nor French. By about 1700, the movement for the use of national languages had reached academia, and an example of the transition is Newtons writing career. A much earlier example is Galileo c,1600, some of whose scientific writings were in Latin, some in Italian, the latter to reach a wider audience. Likewise, in the early 18th century, French replaced Latin as a diplomatic language, at the same time, some were dismissing Latin as a useless accomplishment, unfit for a man of practical affairs. The last international treaty to be written in Latin was the Treaty of Vienna in 1738, a diminishing audience combined with diminishing production of Latin texts pushed Latin into a declining spiral from which it has not recovered

10.
French language
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French is a Romance language of the Indo-European family. It descended from the Vulgar Latin of the Roman Empire, as did all Romance languages, French has evolved from Gallo-Romance, the spoken Latin in Gaul, and more specifically in Northern Gaul. Its closest relatives are the other langues doïl—languages historically spoken in northern France and in southern Belgium, French was also influenced by native Celtic languages of Northern Roman Gaul like Gallia Belgica and by the Frankish language of the post-Roman Frankish invaders. Today, owing to Frances past overseas expansion, there are numerous French-based creole languages, a French-speaking person or nation may be referred to as Francophone in both English and French. French is a language in 29 countries, most of which are members of la francophonie. As of 2015, 40% of the population is in Europe, 35% in sub-Saharan Africa, 15% in North Africa and the Middle East, 8% in the Americas. French is the fourth-most widely spoken mother tongue in the European Union, 1/5 of Europeans who do not have French as a mother tongue speak French as a second language. As a result of French and Belgian colonialism from the 17th and 18th century onward, French was introduced to new territories in the Americas, Africa, most second-language speakers reside in Francophone Africa, in particular Gabon, Algeria, Mauritius, Senegal and Ivory Coast. In 2015, French was estimated to have 77 to 110 million native speakers, approximately 274 million people are able to speak the language. The Organisation internationale de la Francophonie estimates 700 million by 2050, in 2011, Bloomberg Businessweek ranked French the third most useful language for business, after English and Standard Mandarin Chinese. Under the Constitution of France, French has been the language of the Republic since 1992. France mandates the use of French in official government publications, public education except in specific cases, French is one of the four official languages of Switzerland and is spoken in the western part of Switzerland called Romandie, of which Geneva is the largest city. French is the language of about 23% of the Swiss population. French is also a language of Luxembourg, Monaco, and Aosta Valley, while French dialects remain spoken by minorities on the Channel Islands. A plurality of the worlds French-speaking population lives in Africa and this number does not include the people living in non-Francophone African countries who have learned French as a foreign language. Due to the rise of French in Africa, the total French-speaking population worldwide is expected to reach 700 million people in 2050, French is the fastest growing language on the continent. French is mostly a language in Africa, but it has become a first language in some urban areas, such as the region of Abidjan, Ivory Coast and in Libreville. There is not a single African French, but multiple forms that diverged through contact with various indigenous African languages, sub-Saharan Africa is the region where the French language is most likely to expand, because of the expansion of education and rapid population growth

11.
Russian language
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Russian is an East Slavic language and an official language in Russia, Belarus, Kazakhstan, Kyrgyzstan and many minor or unrecognised territories. Russian belongs to the family of Indo-European languages and is one of the four living members of the East Slavic languages, written examples of Old East Slavonic are attested from the 10th century and beyond. It is the most geographically widespread language of Eurasia and the most widely spoken of the Slavic languages and it is also the largest native language in Europe, with 144 million native speakers in Russia, Ukraine and Belarus. Russian is the eighth most spoken language in the world by number of native speakers, the language is one of the six official languages of the United Nations. Russian is also the second most widespread language on the Internet after English, Russian distinguishes between consonant phonemes with palatal secondary articulation and those without, the so-called soft and hard sounds. This distinction is found between pairs of almost all consonants and is one of the most distinguishing features of the language, another important aspect is the reduction of unstressed vowels. Russian is a Slavic language of the Indo-European family and it is a lineal descendant of the language used in Kievan Rus. From the point of view of the language, its closest relatives are Ukrainian, Belarusian, and Rusyn. An East Slavic Old Novgorod dialect, although vanished during the 15th or 16th century, is considered to have played a significant role in the formation of modern Russian. In the 19th century, the language was often called Great Russian to distinguish it from Belarusian, then called White Russian and Ukrainian, however, the East Slavic forms have tended to be used exclusively in the various dialects that are experiencing a rapid decline. In some cases, both the East Slavic and the Church Slavonic forms are in use, with different meanings. For details, see Russian phonology and History of the Russian language and it is also regarded by the United States Intelligence Community as a hard target language, due to both its difficulty to master for English speakers and its critical role in American world policy. The standard form of Russian is generally regarded as the modern Russian literary language, mikhail Lomonosov first compiled a normalizing grammar book in 1755, in 1783 the Russian Academys first explanatory Russian dictionary appeared. By the mid-20th century, such dialects were forced out with the introduction of the education system that was established by the Soviet government. Despite the formalization of Standard Russian, some nonstandard dialectal features are observed in colloquial speech. Thus, the Russian language is the 6th largest in the world by number of speakers, after English, Mandarin, Hindi/Urdu, Spanish, Russian is one of the six official languages of the United Nations. Education in Russian is still a choice for both Russian as a second language and native speakers in Russia as well as many of the former Soviet republics. Russian is still seen as an important language for children to learn in most of the former Soviet republics, samuel P. Huntington wrote in the Clash of Civilizations, During the heyday of the Soviet Union, Russian was the lingua franca from Prague to Hanoi

12.
Spanish language
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Spanish —also called Castilian —is a Romance language that originated in the Castile region of Spain, with hundreds of millions of native speakers around the world. It is usually considered the worlds second-most spoken native language after Mandarin Chinese and it is one of the few languages to use inverted question and exclamation marks. Spanish is a part of the Ibero-Romance group of languages, which evolved from several dialects of Vulgar Latin in Iberia after the collapse of the Western Roman Empire in the 5th century. Beginning in the early 16th century, Spanish was taken to the colonies of the Spanish Empire, most notably to the Americas, as well as territories in Africa, Oceania, around 75% of modern Spanish is derived from Latin. Greek has also contributed substantially to Spanish vocabulary, especially through Latin, Spanish vocabulary has been in contact from an early date with Arabic, having developed during the Al-Andalus era in the Iberian Peninsula. With around 8% of its vocabulary being Arabic in origin, this language is the second most important influence after Latin and it has also been influenced by Basque as well as by neighboring Ibero-Romance languages. It also adopted words from languages such as Gothic language from the Visigoths in which many Spanish names and surnames have a Visigothic origin. Spanish is one of the six languages of the United Nations. It is the language in the world by the number of people who speak it as a mother tongue, after Mandarin Chinese. It is estimated more than 437 million people speak Spanish as a native language. Spanish is the official or national language in Spain, Equatorial Guinea, speakers in the Americas total some 418 million. In the European Union, Spanish is the tongue of 8% of the population. Spanish is the most popular second language learned in the United States, in 2011 it was estimated by the American Community Survey that of the 55 million Hispanic United States residents who are five years of age and over,38 million speak Spanish at home. The Spanish Constitution of 1978 uses the term castellano to define the language of the whole Spanish State in contrast to las demás lenguas españolas. Article III reads as follows, El castellano es la lengua española oficial del Estado, las demás lenguas españolas serán también oficiales en las respectivas Comunidades Autónomas. Castilian is the official Spanish language of the State, the other Spanish languages as well shall be official in their respective Autonomous Communities. The Spanish Royal Academy, on the hand, currently uses the term español in its publications. Two etymologies for español have been suggested, the Spanish Royal Academy Dictionary derives the term from the Provençal word espaignol, and that in turn from the Medieval Latin word Hispaniolus, from—or pertaining to—Hispania

13.
Modern Standard Arabic
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Modern Standard Arabic, Standard Arabic, or Literary Arabic is the standardized and literary variety of Arabic used in writing and in most formal speech. It is considered a pluricentric language, MSA is based on classical Arabic, and differences between the two varieties of the language are directly related to modernizing and simplification, both in speaking and writing styles. Classical Arabic, also known as Quranic Arabic, is the used in the Quran as well as in numerous literary texts from Umayyad. Many Muslims study Classical Arabic in order to read the Quran in its original language, Modern Standard Arabic is the literary standard across the Middle East, North Africa, Horn of Africa and is one of the six official languages of the United Nations. Most printed matter in the Arab League—including most books, newspapers, magazines, official documents and they are not normally written, although a certain amount of literature exists in many of them. Literary Arabic is the language of all Arab League countries and is the only form of Arabic taught in schools at all stages. Additionally, some Christian Arabic speakers recite prayers in it, as it is considered the literary language and this diglossic situation facilitates code-switching in which a speaker switches back and forth between the two dialects of the language, sometimes even within the same sentence. People speak MSA as a language if they speak other languages native to a country as their first language. Modern Standard Arabic is also spoken by people of Arab descent outside the Arab world when people of Arab descent speaking different dialects communicate each other, as there is a prestige or standard dialect of vernacular Arabic, speakers of standard colloquial dialects code-switch between these particular dialects and MSA. For these reasons, Modern Standard Arabic is generally treated separately in non-Arab sources, Arabic sources generally tend to regard MSA and Classical Arabic as different registers of one and the same language. Speakers of Modern Standard Arabic do not always observe the rules of Classical Arabic grammar. On the whole, Modern Standard Arabic is not homogeneous, there are authors who write in a very close to the classical models. As MSA is a revised and simplified form of Classical Arabic, as diglossia is involved, various Arabic dialects freely borrow words from MSA, this situation is similar to Romance languages, wherein scores of words were borrowed directly from formal Latin. It depends on the knowledge and attitude to the grammar of Classical Arabic, as well as the region. Pronunciation of foreign names in MSA is loose, names can be pronounced or even spelled differently in different regions, pronunciation also depends on the persons education, linguistic knowledge and abilities. Modern languages have also influenced pronunciation or word order. Examples are Turkish and English in Egypt, French in North Africa, Lebanon and Syria, English and Hebrew in Israel, notes, the marginal phoneme /ɫ/ only occurs in the word الله /aɫːaːh/ and words derived from it. /u/ can also have different realizations, i. e and they are distinct phonemes in loan words

14.
Standard Chinese
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Its pronunciation is based on the Beijing dialect, its vocabulary on the Mandarin dialects, and its grammar is based on written vernacular Chinese. Like other varieties of Chinese, Standard Chinese is a language with topic-prominent organization. It has more initial consonants but fewer vowels, final consonants, Standard Chinese is an analytic language, though with many compound words. There exist two standardised forms of the language, namely Putonghua in Mainland China and Guoyu in Taiwan, aside from a number of differences in pronunciation and vocabulary, Putonghua is written using simplified Chinese characters, while Guoyu is written using traditional Chinese characters. There are many characters that are identical between the two systems, in English, the governments of China and Hong Kong use Putonghua, Putonghua Chinese, Mandarin Chinese, and Mandarin, while those of Taiwan, Singapore, and Malaysia, use Mandarin. The name Putonghua also has a long, albeit unofficial, history and it was used as early as 1906 in writings by Zhu Wenxiong to differentiate a modern, standard Chinese from classical Chinese and other varieties of Chinese. For some linguists of the early 20th century, the Putonghua, or common tongue/speech, was different from the Guoyu. The former was a prestige variety, while the latter was the legal standard. Based on common understandings of the time, the two were, in fact, different, Guoyu was understood as formal vernacular Chinese, which is close to classical Chinese. By contrast, Putonghua was called the speech of the modern man. The use of the term Putonghua by left-leaning intellectuals such as Qu Qiubai, prior to this, the government used both terms interchangeably. In Taiwan, Guoyu continues to be the term for Standard Chinese. The term Putonghua, on the contrary, implies nothing more than the notion of a lingua franca, Huayu, or language of the Chinese nation, originally simply meant Chinese language, and was used in overseas communities to contrast Chinese with foreign languages. Over time, the desire to standardise the variety of Chinese spoken in these communities led to the adoption of the name Huayu to refer to Mandarin and it also incorporates the notion that Mandarin is usually not the national or common language of the areas in which overseas Chinese live. The term Mandarin is a translation of Guānhuà, which referred to the lingua franca of the late Chinese empire, in English, Mandarin may refer to the standard language, the dialect group as a whole, or to historic forms such as the late Imperial lingua franca. The name Modern Standard Mandarin is sometimes used by linguists who wish to distinguish the current state of the language from other northern. Chinese has long had considerable variation, hence prestige dialects have always existed. Confucius, for example, used yǎyán rather than colloquial regional dialects, rime books, which were written since the Northern and Southern dynasties, may also have reflected one or more systems of standard pronunciation during those times

15.
Angiogenesis
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Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels. The first vessels in the embryo form through vasculogenesis, after which angiogenesis is responsible for most, if not all, blood vessel growth during development. Angiogenesis is a normal and vital process in growth and development, as well as in wound healing and in the formation of granulation tissue. However, it is also a step in the transition of tumors from a benign state to a malignant one. Sprouting angiogenesis was the first identified form of angiogenesis and it occurs in several well-characterized stages. First, biological signals known as growth factors activate receptors on endothelial cells present in pre-existing blood vessels. Second, the endothelial cells begin to release enzymes called proteases that degrade the basement membrane to allow endothelial cells to escape from the original vessel walls. The endothelial cells then proliferate into the matrix and form solid sprouts connecting neighboring vessels. As sprouts extend toward the source of the stimulus, endothelial cells migrate in tandem. These sprouts then form loops to become a full-fledged vessel lumen as cells migrate to the site of angiogenesis, sprouting occurs at a rate of several millimeters per day, and enables new vessels to grow across gaps in the vasculature. It is markedly different from splitting angiogenesis because it forms new vessels as opposed to splitting existing vessels. By intussusception, also known as splitting angiogenesis, a new vessel is created by splitting of an existing blood vessel in two. Intussusception was first observed in neonatal rats, in this type of vessel formation, the capillary wall extends into the lumen to split a single vessel in two. There are four phases of intussusceptive angiogenesis, first, the two opposing capillary walls establish a zone of contact. Second, the endothelial cell junctions are reorganized and the vessel bilayer is perforated to allow growth factors, third, a core is formed between the 2 new vessels at the zone of contact that is filled with pericytes and myofibroblasts. These cells begin laying collagen fibers into the core to provide a matrix for growth of the vessel lumen. Finally, the core is fleshed out with no alterations to the basic structure, intussusception is important because it is a reorganization of existing cells. It allows a vast increase in the number of capillaries without an increase in the number of endothelial cells

16.
Serotonin
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Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is found in the gastrointestinal tract, blood platelets. It is popularly thought to be a contributor to feelings of well-being, approximately 90% of the human bodys total serotonin is located in the enterochromaffin cells in the GI tract, where it is used to regulate intestinal movements. The remainder is synthesized in serotonergic neurons of the CNS, where it has various functions and these include the regulation of mood, appetite, and sleep. Serotonin also has some functions, including memory and learning. Modulation of serotonin at synapses is thought to be an action of several classes of pharmacological antidepressants. Serotonin secreted from the cells eventually finds its way out of tissues into the blood. There, it is taken up by blood platelets, which store it. When the platelets bind to a clot, they release serotonin, Serotonin is also a growth factor for some types of cells, which may give it a role in wound healing. Serotonin is metabolized mainly to 5-HIAA, chiefly by the liver, metabolism involves first oxidation by monoamine oxidase to the corresponding aldehyde. This is followed by oxidation by aldehyde dehydrogenase to 5-HIAA, the acetic acid derivative. The latter is then excreted by the kidneys, in addition to animals, serotonin is found in fungi and plants. Serotonins presence in insect venoms and plant spines serves to cause pain, Serotonin is produced by pathogenic amoebae, and its effect on the gut causes diarrhea. Its widespread presence in many seeds and fruits may serve to stimulate the digestive tract into expelling the seeds, Serotonin is a neurotransmitter and is found in all bilateral animals, where it mediates gut movements and the animals perceptions of resource availability. In less complex animals, such as invertebrates, resources simply mean food availability. In more complex animals, such as arthropods and vertebrates, resources also can mean social dominance, in response to the perceived abundance or scarcity of resources, an animals growth, reproduction or mood may be elevated or lowered. This may somewhat depend on how much serotonin the organism has at its disposal, except for the 5-HT3 receptor, a ligand-gated ion channel, all other 5-HT receptors are G-protein-coupled receptors that activate an intracellular second messenger cascade. Serotonergic action is terminated primarily via uptake of 5-HT from the synapse and this is accomplished through the specific monoamine transporter for 5-HT, SERT, on the presynaptic neuron

17.
Ritanserin
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Ritanserin is a serotonin receptor antagonist which was never marketed for clinical use but has been used in scientific research. Ritanserin was tested in trials for schizophrenia and migraine. Ritanserin acts as a selective 5-HT2A and 5-HT2C receptor antagonist and it has relatively low affinity for the H1, D2, α1-adrenergic, and α2-adrenergic receptors. The affinity of ritanserin for the 5-HT1A receptor is than 1 µM, in addition to its affinity for the 5-HT2A and 5-HT2C receptors, ritanserin also binds to and antagonizes the 5-HT1D, 5-HT2B, 5-HT5A, 5-HT6, and 5-HT7 receptors. The atypical antipsychotic risperidone was developed from ritanserin

18.
Mianserin
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Mianserin is a psychoactive drug of the tetracyclic antidepressant therapeutic family. It is classified as a noradrenergic and specific serotonergic antidepressant and has antidepressant, anxiolytic, hypnotic, antiemetic, orexigenic and it is not approved for use in the US, but its analogue, mirtazapine, is. Mianserin was the first antidepressant to reach the UK market that was less dangerous than the tricyclic antidepressants in overdose, mianserin received TGA approval in May 1996. Similarly to its analogue, mirtazapine, mianserin has been tried as a strategy in treatment-resistant depression with some success. Mianserin has been tried, similarly to mirtazapine, as an adjunct in schizophrenia and has found to reduce negative and cognitive symptoms. Mianserin has demonstrated efficacy as a monotherapy for the treatment of Parkinsons disease psychosis in a clinical trial. Rare adverse effects include Oedema — the swelling of the bodys tissues due to fluid draining into said tissues, arthralgia Arthritis Rash Akathisia — a sense of inner restlessness that is often distressing for patients. Some cases of mianserin-induced blood dyscrasias have been fatal, gynaecomastia — abnormal breast enlargement in males. Pruritus — itchiness Hypertension Tachycardia Tinnitus — hearing ringing in the ears in the absence of an actual sound, conversely, CYP2D6 inducers would likely lead to reduced mianserin plasma concentrations and hence potentially diminish the therapeutic effects of mianserin. As a high affinity H1 receptor inverse agonist, mianserin has strong antihistamine effects, contrarily, it has negligible affinity for the mACh receptors, and thus lacks anticholinergic properties. It was recently found to be a weak κ-opioid receptor partial agonist, in addition, mianserin also appears to be a potent antagonist of the neuronal octopamine receptor. --Mianserin is approximately 200–300 times more active than its enantiomer --mianserin

19.
Enzyme
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Enzymes /ˈɛnzaɪmz/ are macromolecular biological catalysts. Enzymes accelerate, or catalyze, chemical reactions, the molecules at the beginning of the process upon which enzymes may act are called substrates and the enzyme converts these into different molecules, called products. Almost all metabolic processes in the cell need enzymes in order to occur at rates fast enough to sustain life, the set of enzymes made in a cell determines which metabolic pathways occur in that cell. The study of enzymes is called enzymology, enzymes are known to catalyze more than 5,000 biochemical reaction types. Most enzymes are proteins, although a few are catalytic RNA molecules, enzymes specificity comes from their unique three-dimensional structures. Like all catalysts, enzymes increase the rate of a reaction by lowering its activation energy, some enzymes can make their conversion of substrate to product occur many millions of times faster. An extreme example is orotidine 5-phosphate decarboxylase, which allows a reaction that would take millions of years to occur in milliseconds. Chemically, enzymes are like any catalyst and are not consumed in chemical reactions, enzymes differ from most other catalysts by being much more specific. Enzyme activity can be affected by other molecules, inhibitors are molecules that decrease enzyme activity, many drugs and poisons are enzyme inhibitors. An enzymes activity decreases markedly outside its optimal temperature and pH, some enzymes are used commercially, for example, in the synthesis of antibiotics. French chemist Anselme Payen was the first to discover an enzyme, diastase and he wrote that alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells. In 1877, German physiologist Wilhelm Kühne first used the term enzyme, the word enzyme was used later to refer to nonliving substances such as pepsin, and the word ferment was used to refer to chemical activity produced by living organisms. Eduard Buchner submitted his first paper on the study of yeast extracts in 1897, in a series of experiments at the University of Berlin, he found that sugar was fermented by yeast extracts even when there were no living yeast cells in the mixture. He named the enzyme that brought about the fermentation of sucrose zymase, in 1907, he received the Nobel Prize in Chemistry for his discovery of cell-free fermentation. Following Buchners example, enzymes are usually named according to the reaction they carry out, the biochemical identity of enzymes was still unknown in the early 1900s. Sumner showed that the enzyme urease was a protein and crystallized it. These three scientists were awarded the 1946 Nobel Prize in Chemistry, the discovery that enzymes could be crystallized eventually allowed their structures to be solved by x-ray crystallography. This high-resolution structure of lysozyme marked the beginning of the field of structural biology, an enzymes name is often derived from its substrate or the chemical reaction it catalyzes, with the word ending in -ase

20.
Tissue plasminogen activator
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Tissue plasminogen activator is a protein involved in the breakdown of blood clots. It is a protease found on endothelial cells, the cells that line the blood vessels. As an enzyme, it catalyzes the conversion of plasminogen to plasmin, because it works on the clotting system, tPA is used in clinical medicine to treat embolic or thrombotic stroke. Use is contraindicated in hemorrhagic stroke and head trauma, the antidote for tPA in case of toxicity is aminocaproic acid. TPA may be manufactured using recombinant biotechnology techniques, TPA created this way may be referred to as recombinant tissue plasminogen activator. TPA is used in cases of diseases that feature blood clots, such as pulmonary embolism, myocardial infarction. The most common use is for ischemic stroke, there have been twelve large scale, high-quality trials of rtPA in acute ischemic stroke. It has been suggested that if tPA is effective in ischemic stroke, indeed, tPA has become widely considered standard of care in acute ischemic stroke, so long as the patient presents soon after the onset of stroke symptoms. Protocol guidelines require its use intravenously within the first three hours of the event, after which its detriments may outweigh its benefits, delayed presentation to the ED leads to decreased eligibility, as few as 3% of people qualify for this treatment. Similarly in the United States, the window of administration used to be 3 hours from onset of symptoms, TPA appears to show benefit not only for large artery occlusions but also for lacunar strokes. Since tPA dissolves blood clots, there is risk of hemorrhage with its use, use on patients with mild deficits, of nonwhite race/ethnicity, and oldest old age increased. However, many patients who were eligible for treatment were not treated, TPA has also been given to patients with acute ischemic stroke above age 90 years old. Although a small fraction of patients 90 years and above treated with tPA for acute ischemic stroke recover, nonagenarians may do as well as octogenarians following treatment with IV-tPA for acute ischemic stroke. In addition, people with frostbite treated with tPA had fewer amputations than those not treated with tPA, there is consensus amongst stroke specialists that tPA is the standard of care for eligible stroke patients and benefits outweigh the risks. There is significant debate mainly in the emergency medicine community regarding recombinant tPAs effectiveness in ischemic stroke, the NNT Group on evidence-based medicine concluded that it was inappropriate to combine these twelve trials into a single analysis, because of substantial clinical heterogeneity. On the basis of evidence, the NNT Group recommended against the use of tPA in acute ischaemic stroke. Indeed, even the original publication of the IST-3 trial found that time-window effects were not significant predictors of outcome, in the UK, concerns by stroke specialists have led to a review by the Medicines and Healthcare products Regulatory Agency. Pulmonary embolism is usually treated with heparin generally followed by warfarin, if pulmonary embolism causes severe instability due to high pressure on the heart and leads to low blood pressure, recombinant tPA is recommended

21.
Benzodiazepine
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Benzodiazepines, sometimes called benzos, are a class of psychoactive drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. In 1977 benzodiazepines were globally the most prescribed medications, Benzodiazepines enhance the effect of the neurotransmitter gamma-aminobutyric acid at the GABAA receptor, resulting in sedative, hypnotic, anxiolytic, anticonvulsant, and muscle relaxant properties. High doses of many shorter-acting benzodiazepines may also cause anterograde amnesia and these properties make benzodiazepines useful in treating anxiety, insomnia, agitation, seizures, muscle spasms, alcohol withdrawal and as a premedication for medical or dental procedures. Benzodiazepines are categorized as either short-, intermediate-, or long-acting, short- and intermediate-acting benzodiazepines are preferred for the treatment of insomnia, longer-acting benzodiazepines are recommended for the treatment of anxiety. Benzodiazepines are generally viewed as safe and effective for use, although cognitive impairment. A minority of people can have paradoxical reactions such as worsened agitation or panic, long-term use is controversial because of concerns about adverse psychological and physical effects, decreasing effectiveness, and physical dependence and withdrawal. As a result of adverse effects associated with the use of benzodiazepines, withdrawal from benzodiazepines, in general. There is controversy concerning the safety of benzodiazepines in pregnancy, Benzodiazepines can be taken in overdoses and can cause dangerous deep unconsciousness. However, they are less toxic than their predecessors, the barbiturates, when combined with other central nervous system depressants such as ethanol and opioids, the potential for toxicity and fatal overdose increases. Benzodiazepines are commonly misused and taken in combination with other drugs of abuse, most are administered orally, however, they can also be given intravenously, intramuscularly, or rectally. In general, benzodiazepines are well-tolerated and are safe and effective drugs in the term for a wide range of conditions. Tolerance can develop to their effects and there is also a risk of dependence and these factors, combined with other possible secondary effects after prolonged use such as psychomotor, cognitive, or memory impairments, limit their long-term applicability. The effects of use or misuse include the tendency to cause or worsen cognitive deficits, depression. The College of Physicians and Surgeons of British Columbia recommends discontinuing the usage of benzodiazepines in those on opioids, because of their effectiveness, tolerability, and rapid onset of anxiolytic action, benzodiazepines are frequently used for the treatment of anxiety associated with panic disorder. However, there is disagreement among expert bodies regarding the use of benzodiazepines for panic disorder. APA states that there is insufficient evidence to recommend any of the established panic disorder treatments over another, one advantage of benzodiazepines is that they alleviate the anxiety symptoms much faster than antidepressants, and therefore may be preferred in patients for whom rapid symptom control is critical. However, this advantage is offset by the possibility of developing benzodiazepine dependence, APA does not recommend benzodiazepines for persons with depressive symptoms or a recent history of substance abuse. Although major concerns about benzodiazepine tolerance and withdrawal have been raised, for many such patients stable doses of benzodiazepines retain their efficacy over several years

22.
Oxazepam
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Oxazepam is used for the treatment of anxiety and insomnia and in the control of symptoms of alcohol withdrawal. Oxazepam was initially patented and marketed in 1965 and it is an intermediate-acting benzodiazepine with a slow onset of action, so it is usually prescribed to individuals who have trouble staying asleep, rather than falling asleep. It is commonly prescribed for anxiety disorders with associated tension, irritability and it is also prescribed for drug and alcohol withdrawal, and for anxiety associated with depression. Physicians may use oxazepam outside its approved indications to treat social phobia, post-traumatic stress disorder, insomnia, premenstrual syndrome, Oxazepam, as with other benzodiazepine drugs, can cause tolerance, physical dependence, addiction, and benzodiazepine withdrawal syndrome. Withdrawal from oxazepam or other benzodiazepines often leads to withdrawal symptoms which are similar to those seen during alcohol, the higher the dose and the longer the drug is taken, the greater the risk of experiencing unpleasant withdrawal symptoms. Withdrawal symptoms can occur, though, at standard dosages and also after short-term use, benzodiazepine treatment should be discontinued as soon as possible by a slow and gradual dose reduction regimen. Oxazepam is contraindicated in myasthenia gravis, chronic obstructive pulmonary disease, benzodiazepines require special precautions if used in the elderly, during pregnancy, in children, alcohol- or drug-dependent individuals, and individuals with comorbid psychiatric disorders. Benzodiazepines including oxazepam are lipophilic drugs and rapidly penetrate membranes, so rapidly crosses over into the placenta with significant uptake of the drug, use of benzodiazepines in late pregnancy, especially high doses, may result in floppy infant syndrome. Floppy infant syndrome and sedation in the newborn may also occur, symptoms of floppy infant syndrome and the neonatal benzodiazepine withdrawal syndrome have been reported to persist from hours to months after birth. As oxazepam is a metabolite of diazepam, an overlap in possible interactions is likely with other drugs or food. Precautions and following the prescription are required when taking oxazepam in combinations with antidepressant medication, concurrent use of these medicines can interact in a way that is difficult to predict. Drinking alcohol when taking oxazepam is not recommended, Oxazepam is generally less toxic in overdose than other benzodiazepines. Important factors which affect the severity of a benzodiazepine overdose include the dose ingested, the age of the patient, benzodiazepine overdoses can be much more dangerous if a coingestion of other CNS depressants such as opiates or alcohol has occurred. The half-life of oxazepam is four to 15 hours and it has been shown to suppress cortisol levels. Oxazepam is the most slowly absorbed and has the slowest onset of action of all the common benzodiazepines according to one British study, Oxazepam is an active metabolite formed during the breakdown of diazepam, nordazepam, and certain similar drugs. Oxazepam is similar to lorazepam in this respect, preferential storage of oxazepam occurs in some organs, including the heart of the neonate. Oxazepam exists as a racemic mixture, early attempts to isolate enantiomers were unsuccessful, the corresponding acetate has been isolated as a single enantiomer. Oxazepam has the potential for misuse, defined as taking the drug to achieve a high, benzodiazepines, including diazepam, oxazepam, nitrazepam, and flunitrazepam, accounted for the largest volume of forged drug prescriptions in Sweden from 1982 to 1986

23.
Local anesthetic
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A local anesthetic is a medication that causes reversible absence of pain sensation, although other senses are often affected, as well. Also, when it is used on specific nerve pathways, paralysis also can be achieved, clinical LAs belong to one of two classes, aminoamide and aminoester local anesthetics. Synthetic LAs are structurally related to cocaine and they differ from cocaine mainly in that they have a very low abuse potential and do not produce hypertension or vasoconstriction. In a medical setting, pain alleviation is desired when its function is no longer needed. Besides improving patient comfort, pain therapy can also reduce harmful physiological consequences of untreated pain, acute pain can often be managed using analgesics. However, conduction anesthesia may be preferable because of pain control. For purposes of pain therapy, LA drugs are given by repeated injection or continuous infusion through a catheter. Low doses of LA drugs can be sufficient so that muscle weakness does not occur, LAs can be applied repeatedly or continuously for prolonged periods to relieve chronic pain, usually in combination with medication such as opioids, NSAIDs, and anticonvulsants. Virtually every part of the body can be anesthetized using conduction anesthesia, however, only a limited number of techniques are in common clinical use. Sometimes, conduction anesthesia is combined with general anesthesia or sedation for the patients comfort and it may also be suitable for other kinds of punctures such as ascites drainage and amniocentesis. Surface anesthesia also facilitates some endoscopic procedures such as bronchoscopy or cystoscopy, the local adverse effects of anesthetic agents include neurovascular manifestations such as prolonged anesthesia and paresthesia. These are symptoms of localized nerve impairment or nerve damage, of particular note, the use of topical anesthetics for relief of eye pain can result in severe corneal damage. The risk of temporary or permanent nerve damage varies between different locations and types of nerve blocks, permanent nerve damage after a peripheral nerve block is rare. Symptoms are likely to resolve within a few weeks, the vast majority of those affected recover within four to six weeks, 99% of these people have recovered within a year. An estimated one in 5,000 to 30,000 nerve blocks results in degree of permanent persistent nerve damage. Symptoms may continue to improve for up to 18 months following injury, the conduction of electric impulses follows a similar mechanism in peripheral nerves, the central nervous system, and the heart. The effects of local anesthetics are, therefore, not specific for the conduction in peripheral nerves. Side effects on the nervous system and the heart may be severe

24.
Procaine
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Procaine is a local anesthetic drug of the amino ester group. It is used primarily to reduce the pain of intramuscular injection of penicillin, owing to the ubiquity of the trade name Novocain, in some regions, procaine is referred to generically as novocaine. It acts mainly as a channel blocker. Today it is used therapeutically in some countries due to its sympatholytic, anti-inflammatory, perfusion-enhancing, procaine was first synthesized in 1905, shortly after amylocaine. It was created by the German chemist Alfred Einhorn who gave the chemical the trade name Novocaine, from the Latin nov- and -caine and it was introduced into medical use by surgeon Heinrich Braun. Prior to the discovery of amylocaine and procaine, cocaine was the most commonly used local anesthetic, Einhorn wished his new discovery to be used for amputations, but surgeons preferred general anesthetic. Dentists, however, found it very useful, the primary use for procaine is as an anaesthetic. Procaine is used frequently today since more effective alternatives such as lidocaine exist. Like other local anesthetics, procaine is a vasodilator, thus is often coadministered with epinephrine for the purpose of vasoconstriction, unlike cocaine, a vasoconstrictor, procaine does not have the euphoric and addictive qualities that put it at risk for abuse. Procaine, an anesthetic, is metabolized in the plasma by the enzyme pseudocholinesterase through hydrolysis into para-amino benzoic acid. Procaine is the ingredient in the controversial preparation Gerovital H3 by Ana Aslan. The mainstream medical view is that claims were seriously studied and discredited in the 1960s. A 1% procaine injection has been recommended for the treatment of extravasation complications associated with venipuncture and it has likewise been recommended for treatment of inadvertent intra-arterial injections, as it helps relieve pain and vascular spasm. Procaine is an additive in illicit street drugs, such as cocaine. MDMA manufacturers also use procaine as an additive at ratios ranging from 1,1 up to 10% MDMA with 90% procaine, application of procaine leads to the depression of neuronal activity. The depression causes the system to become hypersensitive, producing restlessness. Studies on animals have shown the use of procaine led to the increase of dopamine, other issues may occur because of varying individual tolerance to procaine dosage. Nervousness and dizziness can arise from the excitation of the nervous system

25.
Cocaine
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Cocaine, also known as coke, is a strong stimulant mostly used as a recreational drug. It is commonly snorted, inhaled, or injected into the veins, mental effects may include loss of contact with reality, an intense feeling of happiness, or agitation. Physical symptoms may include a fast heart rate, sweating, high doses can result in very high blood pressure or body temperature. Effects begin within seconds to minutes of use and last between five and ninety minutes, Cocaine has a small number of accepted medical uses such as numbing and decreasing bleeding during nasal surgery. Cocaine is addictive due to its effect on the pathway in the brain. After a short period of use, there is a risk that dependence will occur. Its use also increases the risk of stroke, myocardial infarction, lung problems in those who smoke it, blood infections, Cocaine sold on the street is commonly mixed with local anesthetics, cornstarch, quinine, or sugar which can result in additional toxicity. Following repeated doses a person may have decreased ability to feel pleasure, Cocaine acts by inhibiting the reuptake of serotonin, norepinephrine, and dopamine. This results in concentrations of these three neurotransmitters in the brain. It can easily cross the barrier and may lead to the breakdown of the barrier. Cocaine is made from the leaves of the plant which are mostly grown in South America. In 2013,419 kilograms were produced legally and it is estimated that the illegal market for cocaine is 100 to 500 billion USD each year. With further processing crack cocaine can be produced from cocaine, after cannabis, cocaine is the most frequently used illegal drug globally. Between 14 and 21 million people use the drug each year, use is highest in North America followed by Europe and South America. Between one and three percent of people in the world have used cocaine at some point in their life. In 2013 cocaine use resulted in 4,300 deaths. The leaves of the plant have been used by Peruvians since ancient times. Cocaine was first isolated from the leaves in 1860, since 1961 the international Single Convention on Narcotic Drugs has required countries to make recreational use of cocaine a crime

26.
Antiarrhythmics
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Many attempts have been made to classify antiarrhythmic agents. The problem arises from the fact many of the antiarrhythmic agents have multiple modes of action. The Singh-Vaughan Williams classification was introduced in 1970, as a doctoral candidate at Oxford University, Dr. Bramah N. Singh determined that amiodarone and sotalol had antiarrhythmic properties and belonged to a new class of antiarrhythmic agents. Singh developed part of the system while working in the lab of Miles Vaughan Williams. Singh subsequently pioneered the use of agents at bedside over the next several decades of practice in the United States. With regards to management of atrial fibrillation, classes I and III are used in control as medical cardioversion agents, while classes II. The five main classes in the Singh-Vaughan Williams classification of antiarrhythmic agents are, Class II agents are anti-sympathetic nervous system agents. Most agents in this class are beta blockers, Class III agents affect potassium efflux. Class IV agents affect calcium channels and the AV node, Class V agents work by other or unknown mechanisms. The class I antiarrhythmic agents interfere with the sodium channel, Class I agents are grouped by what effect they have on the Na+ channel, and what effect they have on cardiac action potentials. Class I agents are called membrane-stabilizing agents, the stabilizing word is used to describe the decrease of excitogenicity of the plasma membrane which is brought about by these agents. Class I agents are divided into three based upon their effect on the length of the action potential. Ia lengthens the action potential Ib shortens the action potential Ic does not significantly affect the action potential Class II agents are conventional beta blockers and they act by blocking the effects of catecholamines at the β1-adrenergic receptors, thereby decreasing sympathetic activity on the heart. These agents are particularly useful in the treatment of supraventricular tachycardias and they decrease conduction through the AV node. Class II agents include atenolol, esmolol, propranolol, and metoprolol, Class III agents predominantly block the potassium channels, thereby prolonging repolarization. Since these agents do not affect the channel, conduction velocity is not decreased. The prolongation of the potential duration and refractory period, combined with the maintenance of normal conduction velocity. The class III agents exhibit reverse-use dependence, inhibiting potassium channels, slowing repolarization, results in slowed atrial-ventricular myocyte repolarization

27.
Procainamide
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Procainamide is a medication of the antiarrhythmic class used for the treatment of cardiac arrhythmias. It is classified by the Vaughan Williams classification system as class Ia, in addition to blocking the INa current, it inhibits the IKr rectifier K+ current. Procainamide is also known to induce a voltage-dependent open channel block on the batrachotoxin -activated sodium channels in cardiomyocytes, for example, it can be used to convert new-onset atrial fibrillation, though it is suboptimal for this purpose. It is administered by mouth, by injection, or intravenously. There are many side effects following the induction of procainamide and these adverse effects are ventricular dysrhythmia, bradycardia, hypotension and shock. The adverse effects occur even more if the daily doses are increased. Procainamide may also lead to drug fever and other allergic responses, there is also a chance that systemic lupus erythematosus occurs, which at the same time leads to polyarthralgia, myalgia and pleurisy. Most of these effects may occur due to the acetylation of procainamide. There is just a line between the plasma concentrations of the therapeutic and toxic effect, therefore a high risk for toxicity. Many symptoms resemble systemic lupus erythematosus because procainamide reactivates hydroxylamine and nitroso metabolites, the hydroxylamine and nitroso metabolites are also toxic to bone marrow cells and can cause agranulocytosis. These metabolites are formed due to the activation of polymorphonuclear leukocytes and these leukocytes release myeloperoxidase and hydrogen peroxide, which oxidize the primary aromatic amine of procainamide to form procainamide hydroxylamine. The release of hydrogen peroxide is also called a respiratory burst, furthermore, the metabolites can be formed by activated neutrophils. These metabolites could then bind to their membranes and cause a release of autoantibodies which would react with the neutrophils. Procainamide hydroxylamine has more cytotoxicity by hindering the response of lymphocytes to T-cell and B-cell mitogens, hydroxylamine can also generate methemoglobin, a protein that could hinder further oxygen exchange. It was also detected that the antiarrhythmic drug procainamide interferes with pacemakers, because a toxic level of procainamide leads to decrease in ventricular conduction velocity and increase of the ventricular refractory period. This results in a disturbance in the membrane potential and leads to a supraventricular tachycardia which induces failure of the pacemaker. Thus, it prolongs QT interval of action potential and increases the risk of torsade de pointes, Procainamide works as an anti-arrhythmic agent and is used to treat cardiac arrhythmia. It induces rapid block of the batrachotoxin -activated sodium channels of the heart muscle, the block is voltage-dependent and can occur from both sides, either from the intracellular or the extracellular side

28.
Prostaglandin-endoperoxide synthase 2
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Prostaglandin-endoperoxide synthase 2, also known as cyclooxygenase-2 or COX-2, is an enzyme that in humans is encoded by the PTGS2 gene. In humans it is one of two cyclooxygenases and it is involved in the conversion of arachidonic acid to prostaglandin H2, an important precursor of prostacyclin, among others. PTGS2 was discovered in 1991 by the Daniel Simmons laboratory at Brigham Young University, PTGS2, converts arachidonic acid to prostaglandin endoperoxide H2. PGHSs are targets for NSAIDs and PTGS2 specific inhibitors called coxibs, each monomer of the enzyme has a peroxidase and a PTGS active site. The PTGS enzymes catalyze the conversion of acid to prostaglandins in a two steps. First, hydrogen is abstracted from carbon 13 of arachidonic acid, second, PGG2 is reduced to PGH2 in the peroxidase active site. The synthesized PGH2 is converted to prostaglandins, prostacyclin, or thromboxane A2 by tissue-specific isomerases, the two 15-HETE stereoisomers have intrinsic biological activities but, perhaps more importantly, can be further metabolized to a major class of agents, the lipoxins. Furthermore, aspirin-treated COX-2 metabolizes arachidonic acid almost exclusively to 15-HETE which product can be metabolized to epi-lipoxins. The lipoxins and epi-lipoxins are potent anti-inflammatory agents and may contribute to the activities of the two COXs as well as to aspirin. COX-2 is naturally inhibited by Calcitriol, the conversion of arachidonic acid to PGG2 can be shown as a series of radical reactions analogous to polyunsaturated fatty acid autoxidation. The 13-pro -hydrogen is abstracted and dioxygen traps the pentadienyl radical at carbon 11, the 11-peroxyl radical cyclizes at carbon 9 and the carbon-centered radical generated at C-8 cyclizes at carbon 12, generating the endoperoxide. The allylic radical generated is trapped by dioxygen at carbon 15 to form the 15- -peroxyl radical, another mechanism in which the 13-pro -hydrogen is deprotonated and the carbanion is oxidized to a radical is theoretically possible. The absence of endoperoxide-containing products derived from 10, 10-difluoroarachidonic acid has been thought to indicate the importance of a C-10 carbocation in PGG2 synthesis, however, the cationic mechanism requires that endoperoxide formation comes before the removal of the 13-pro -hydrogen. This is not consistent with the results of the experiments of arachidonic acid oxygenation. PTGS2 exists as a homodimer, each monomer with a mass of about 70 kDa. The tertiary and quaternary structures of PTGS1 and PTGS2 enzymes are almost identical, each subunit has three different structural domains, a short N-terminal epidermal growth factor domain, an α-helical membrane-binding moiety, and a C-terminal catalytic domain. PTGS enzymes are monotopic membrane proteins, the domain consists of a series of amphipathic α helices with several hydrophobic amino acids exposed to a membrane monolayer. PTGS1 and PTGS2 are bifunctional enzymes that carry out two consecutive chemical reactions in spatially distinct but mechanistically coupled active sites, both the cyclooxygenase and the peroxidase active sites are located in the catalytic domain, which accounts for approximately 80% of the protein

29.
Anti-inflammatory drug
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Nonsteroidal anti-inflammatory drugs are a drug class that groups together drugs that provide analgesic and antipyretic effects, and, in higher doses, anti-inflammatory effects. The term nonsteroidal distinguishes these drugs from steroids, which, among a range of other effects, have a similar eicosanoid-depressing. First used in 1960, the served to distance new drugs from steroid-related iatrogenic tragedies. The most prominent members of group of drugs are aspirin, ibuprofen and naproxen. Paracetamol is generally not considered an NSAID because it has only little anti-inflammatory activity and it treats pain mainly by blocking COX-2 mostly in the central nervous system, but not much in the rest of the body. Most NSAIDs inhibit the activity of cyclooxygenase-1 and cyclooxygenase-2, and thereby the synthesis of prostaglandins, NSAIDs are usually used for the treatment of acute or chronic conditions where pain and inflammation are present. NSAIDs are generally used for the relief of the following conditions, Aspirin. This is useful for the management of arterial thrombosis and prevention of cardiovascular events. Aspirin inhibits platelet aggregation by inhibiting the action of thromboxane A2, NSAIDs are useful in the management of post-operative dental pain following invasive dental procedures such as dental extraction. When not contra-indicated they are favoured over the use of paracetamol alone due to the effect they provide. When used in combination with paracetamol the analgesic effect has proven to be improved. Use of NSAIDs increases risk of having a range of gastrointestinal problems, when NSAIDs are used for pain management after surgery they cause increased risk of kidney problems. An estimated 10–20% of NSAID patients experience dyspepsia, in the 1990s high doses of prescription NSAIDs were associated with serious upper gastrointestinal adverse events, including bleeding. Over the past decade, deaths associated with gastric bleeding have declined, NSAIDs, like all drugs, may interact with other medications. For example, concurrent use of NSAIDs and quinolones may increase the risk of quinolones adverse central nervous system effects, there is an argument over the benefits and risks of NSAIDs for treating chronic musculoskeletal pain. Each drug has a profile and balancing the risk of no treatment with the competing potential risks of various therapies is the clinicians responsibility. If a COX-2 inhibitor is taken, a traditional NSAID should not be taken at the same time, in addition, people on daily aspirin therapy must be careful if they also use other NSAIDs, as these may inhibit the cardioprotective effects of aspirin. Rofecoxib was shown to significantly fewer gastrointestinal adverse drug reactions compared with naproxen

30.
Monoclonal antibody
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Monoclonal antibodies are antibodies that are made by identical immune cells that are all clones of a unique parent cell. Monoclonal antibodies can have monovalent affinity, in that they bind to the same epitope, in contrast, polyclonal antibodies bind to multiple epitopes and are usually made by several different plasma cell lineages. Bispecific monoclonal antibodies can also be engineered, by increasing the therapeutic targets of one single monoclonal antibody to two epitopes, given almost any substance, it is possible to produce monoclonal antibodies that specifically bind to that substance, they can then serve to detect or purify that substance. This has become an important tool in biochemistry, molecular biology, when used as medications, non-proprietary drug names end in -mab and many immunotherapy specialists use the word mab anacronymically. He and Élie Metchnikoff received the 1908 Nobel Prize for Physiology or Medicine for this work, in the 1970s, the B-cell cancer multiple myeloma was known. It was understood that these cancerous B-cells all produce a type of antibody. This was used to study the structure of antibodies, but it was not yet possible to produce antibodies specific to a given antigen. They shared the Nobel Prize in Physiology or Medicine in 1984 for the discovery, in 1988, Greg Winter and his team pioneered the techniques to humanize monoclonal antibodies, eliminating the reactions that many monoclonal antibodies caused in some patients. Monoclonal antibodies are made by cell culture that involves fusing myeloma cells with mouse spleen cells immunized with the desired antigen. Rabbit B-cells can be used to form a rabbit hybridoma, polyethylene glycol is used to fuse adjacent plasma membranes, but the success rate is low, so a selective medium in which only fused cells can grow is used. This is possible because myeloma cells have lost the ability to synthesize hypoxanthine-guanine-phosphoribosyl transferase, the absence of HGPRT is not a problem for these cells unless the de novo purine synthesis pathway is also disrupted. Exposing cells to aminopterin, makes them unable to use the de novo pathway and become fully auxotrophic for nucleic acids, the selective culture medium is called HAT medium because it contains hypoxanthine, aminopterin and thymidine. This medium is selective for fused cells, unfused myeloma cells cannot grow because they lack HGPRT and thus cannot replicate their DNA. Unfused spleen cells cannot grow indefinitely because of their life span. Only fused hybrid cells, referred to as hybridomas, are able to grow indefinitely in the media because the spleen cell partner supplies HGPRT and this mixture of cells is then diluted and clones are grown from single parent cells on microtitre wells. The antibodies secreted by the different clones are then assayed for their ability to bind to the antigen or immuno-dot blot, the most productive and stable clone is then selected for future use. The hybridomas can be grown indefinitely in a cell culture medium. They can also be injected into mice, there, they produce tumors secreting an antibody-rich fluid called ascites fluid

31.
Infliximab
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Infliximab is a chimeric monoclonal antibody biologic drug that works against tumor necrosis factor alpha and is used to treat autoimmune diseases. It is used off-label outside its FDA approval for Behçets disease, Infliximab is administered by intravenous infusion, typically at six- to eight-week intervals. It cannot be given by mouth because the system would destroy the drug. Infliximab works by binding to TNF-α, TNF-α is a chemical messenger and a key part of the autoimmune reaction. In rheumatoid arthritis, infliximab seems to work by preventing TNF-α from binding to its receptor in the cell and it was originally developed in mice as a mouse antibody. Because humans have immune reactions to mouse proteins, the mouse common domains were replaced with similar human antibody domains and they are monoclonal antibodies and have identical structures and affinities to the target. Because they are a combination of mouse and human antibody amino acid sequences, in the United States, Remicade/infliximab can cost $19,000 to $22,000 a year per patient, according to Centocor in 2007. Infliximab biosimilars have been approved in the EU, Japan, three phenotypes, or categories of disease, are present in Crohns disease, stricturing disease, penetrating disease, and inflammatory disease. Infliximab was first used for closure of fistulae in Crohns disease in 1999, in a 94-patient, phase II clinical trial, the researchers showed Infliximab was effective in closing fistulae between the skin and bowel in 56-68% of patients. This final trial resulted in the FDA approval of the drug to treat fistulizing disease, Infliximab has been used to induce and maintain remission in inflammatory Crohns disease. It also showed a mean maintenance of remission from 38 to 54 weeks compared with 21 weeks for patients who received placebo treatment, Crohns patients have flares of their disease between periods of disease quiescence. This has been called the approach to treatment. Infliximab targets TNF, thought to be related to Th1 cytokines. Ulcerative colitis was thought to be a Th2 disease, and infliximab would be of limited use, however, patients with ulcerative colitis have begun to be treated with infliximab on the basis of two large clinical trials conducted in 2005 by Paul Rutgeerts and William Sandborn. At two months, the response was 61-69% for patients treated with infliximab, and 31% for those treated with placebo, in psoriatic arthritis, inhibitors of TNF, such as infliximab, improve the signs and symptoms. Several therapies with modest efficacy have been studied in nail psoriasis, among available agents, higher quality data are available to support the efficacy of cyclosporine and infliximab. The anti-TNF agents are effective for the treatment of enthesitis than traditional agents. Results suggest infliximab is effective for the treatment of dactylitis in PsA and it was approved for treating ankylosing spondylitis, psoriatic arthritis, psoriasis, rheumatoid arthritis

32.
Nomenclature of monoclonal antibodies
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The nomenclature of monoclonal antibodies is a naming scheme for assigning generic, or nonproprietary, names to monoclonal antibodies. An antibody is a protein that is produced in B cells and used by the system of humans. Monoclonal antibodies are those that were produced in cells, often artificially. They have a range of applications including medical uses. This naming scheme is used for both the World Health Organization’s International Nonproprietary Names and the United States Adopted Names for pharmaceuticals, in general, word stems are used to identify classes of drugs, in most cases placed word-finally. All monoclonal antibody names end with the stem -mab, unlike most other pharmaceuticals, monoclonal antibody nomenclature uses different preceding word parts depending on structure and function. These are officially called substems and sometimes erroneously infixes, even by the USAN Council itself, the stem -mab is used for monoclonal antibodies as well as for their fragments, as long as at least one variable domain is included. This is the case for antigen binding fragments and single-chain variable fragments, other antibody parts and antibody mimetics use different naming schemes. The substem preceding the stem denotes the animal from which the antibody is obtained, the first monoclonal antibodies were produced in mice or other non-human organisms. Neither INN nor USAN has ever been requested for antibodies from rats, hamsters and these non-human antibodies are recognized as foreign by the human immune system and may be rapidly cleared from the body, provoke an allergic reaction, or both. To avoid this, parts of the antibody can be replaced with human amino acid sequences, if the constant region is replaced with the human form, the antibody is termed chimeric and the substem used is -xi-. Partly chimeric and partly humanized antibodies use -xizu- and these three substems do not indicate the foreign species used for production. Thus, the human/mouse chimeric antibody basiliximab ends in -ximab just as the human/macaque antibody gomiliximab, rat/mouse hybrid antibodies can be engineered with binding sites for two different antigens. These drugs, termed trifunctional antibodies, have the substem -axo-, the substem preceding the source of the antibody refers to the medicines target. Examples of targets are tumors, organ systems like the circulatory system, the term target does not imply what sort of action the antibody exerts. Therapeutic, prophylactic and diagnostic agents are not distinguished by this nomenclature, in the naming scheme as originally developed, these substems mostly consist of a consonant, a vowel, then another consonant. The final letter may be dropped if the name would be difficult to pronounce otherwise. Examples include -ci- for the system, -li- for the immune system

33.
Protease inhibitor (pharmacology)
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Protease inhibitors are a class of antiviral drugs that are widely used to treat HIV/AIDS and hepatitis C. To reduce this risk it is common to use several different drugs together that are aimed at different targets. Protease inhibitors were the class of antiretroviral drugs developed. The first members of class, saquinavir and ritonavir, were approved in late 1995–1996. Within 2 years, annual deaths from AIDS in the United States fell from over 50,000 to approximately 18,000 Prior to this the death rate had been increasing by approximately 20% each year. The drugs saquinavir, ritonavir, and lopinavir have been found to have anti-malarial properties, a cysteine protease inhibitor drug was found to cure Chagas disease in mice. Researchers are investigating whether protease inhibitors could possibly be used to treat cancer, for example, nelfinavir and atazanavir are able to kill tumor cells in culture. Inhibitors of the proteasome, such as bortezomib are now front-line drugs for the treatment of multiple myeloma, tanomastat is one of the matrix metalloproteinase inhibitors that can be used to treat cancer. Protease inhibitors can cause a syndrome of lipodystrophy, hyperlipidemia, diabetes mellitus type 2 and this lipodystrophy is colloquially known as Crix belly, after indinavir

Monoclonal antibodies (mAb or moAb) are antibodies that are made by identical immune cells that are all clones of a …

A general representation of the method used to produce monoclonal antibodies.

Researchers looking at slides of cultures of cells that make monoclonal antibodies. These are grown in a lab and the researchers are analyzing the products to select the most promising of them.

Monoclonal antibodies can be grown in unlimited quantities in the bottles shown in this picture.

Technician hand-filling wells with a liquid for a research test. This test involves preparation of cultures in which hybrids are grown in large quantities to produce desired antibody. This is effected by fusing myeloma cell and mouselymphocyte to form a hybrid cell (hybridoma).

The energies of the stages of a chemical reaction. Uncatalysed (dashed line), substrates need a lot of activation energy to reach a transition state, which then decays into lower-energy products. When enzyme catalysed (solid line), the enzyme binds the substrates (ES), then stabilizes the transition state (ES‡) to reduce the activation energy required to produce products (EP) which are finally released.

Source substems: sketches of mouse (top left), chimeric (top right), humanized (bottom left), chimeric/humanized (bottom middle), and human (bottom right) monoclonal antibodies. Human parts are shown in brown, non-human parts in blue. The variable domains are the boxes on top of each antibody; the CDRs within these domains are represented as triple loops.

Iobenguane, also known as metaiodobenzylguanidine or mIBG, or MIBG (tradename Adreview) is a radiopharmaceutical, used …

Pheochromocytoma seen as dark sphere in center of the body (it is in the left adrenal gland). Image is by MIBGscintigraphy, with radiation from radioiodine in the MIBG. Two images are seen of the same patient from front and back. Note dark image of the thyroid due to unwanted uptake of iodide radioiodine from breakdown of the pharmaceutical, by the thyroid gland in the neck. Uptake at the side of the head are from the salivary glands. Radioactivity is also seen in the bladder, from normal renal excretion of iodide.

Figure 2. PTGS (COX) enzymes produce PGH2 from AA in 12 two consecutive chemical reactions. PGH2 is converted to other prostanoids (at the bottom) by tissue-specific enzymes called isomerases. In the first step of the reaction, two moles of oxygen are added to arachidonic acid to yield PGG2. This is referred to as the PTGS (COX) reaction. The latter is followed by the peroxidase reaction, which reduces PGG2 to give PGH2. The PTGS (COX) reaction and the peroxidase reaction occur at two different locations in PTGS (COX) enzymes. In addition to prostaglandins, PTGS (COX) enzymes also produce small amounts of mono-oxygenated metabolites of AA called HETEs.